Post-doctoral position at the Laboratory of mechanisms of genetic diversity
Exploiting B cell biology to target B cell lymphoma
A large proportion of non-Hodgkin lymphomas become resistant to the available therapies, so new alternatives are needed. This project will exploit a vulnerability created by the enzyme Activation induced deaminase (AID) in B cell lymphoma and leukemia, to specifically target these cancer cells. The project is based on the observations that ablating the non-essential DNA repair factor Uracil N-glycosylase (UNG) allows AID to produce catastrophic damage at the telomeres,permanently arresting B cell proliferation (Cortizas et al, 2016). The project will :
The project is funded by the Lymphoma and leukemia society of Canada starting in July 2017.
We are looking for a candidate with a recent PhD that have demonstrable experience in the relevant techniques necessary for the project (cell culture, transfection techniques, mouse work) and excellent organizational and communicational skills. Previous experience in immunology or hematological malignancies would be an advantage.
Please, send a statement of interest, CV and two letters of reference (including one from PhD supervisor) to Dr. Javier M Di Noia (email@example.com).
Cortizas, E. M.*, Zahn, A.*, Safavi, S.*, Reed, J. A., Vega, F., Di Noia, J. M.*, & Verdun, R. E.* (2016). UNG protects B cells from AID-induced telomere loss. The Journal of Experimental Medicine, 213(11), 2459–2472.
Zahn, A., Daugan, M., Safavi, S., Godin, D., Cheong, C., Lamarre, A., & Di Noia, J. M. (2013). Separation of Function between Isotype Switching and Affinity Maturation In Vivo during Acute Immune Responses and Circulating Autoantibodies in UNGDeficient Mice. Journal of Immunology, 190(12), 5949–5960.
Other recent work by the lab
Methot et al. (2015). Consecutive interactions with HSP90 and eEF1A underlie a functional maturation and storage pathway of AID in the cytoplasm. The Journal of Experimental Medicine, 212(4), 581–596.
Montamat-Sicotte et al. (2015). HSP90 inhibitors decrease AID levels and activity in mice and in human cells. European Journal of Immunology, 45(8), 2365–2376.
Zahn et al. (2014). Activation induced deaminase C-terminal domain links DNA breaks to end protection and repair during class switch recombination. Proceedings of the National Academy of Sciences of the United States of America, 111(11), E988–97.